Antibiotic Responsive Ulcerative Dermatoses in German Shepherd

Dogs with Mucocutaneous Pyoderma

BASSET, GG BURTON and DC ROBSON

Melbourne Veterinary Referral Centre, Glen Waverley, Victoria 3150

Mucocutaneous pyoderma, a relapsing dermatosis of unknown etiology

that is responsive to antibacterial therapy, may affect the lips, nose, nares,

perioral skin, and less commonly the eyelids, vulva, prepuce and anus. The

clinical appearance of the disease is variable and includes erythema and swelling

that progress to crusting, fissuring, erosion, ulceration and focal depigmentation.

Pain and pruritus are variable. German Shepherd Dogs and their crosses may be

predisposed. There is no age or sex predisposition.

The histopathological pattern of MCP is one of epidermal hyperplasia,

often with superficial postulation and crusting, varying degrees of spongiosis and

neutrophilic exocytosis. There is a superficial band of inflammation with plasma

cells predominating in varying numbers of lymphocytes, neutriphils, and

macrophages; however the dermo-epidermal junction is not usually obscured.

Pigmentary incontinence may be marked and periadnexal inflammation can

occur in the adjacent follicular skin. There may be erosion and ulceration and a

dense superficial dermal infiltrate of neutrophils in areas complicated by self-

trauma.

The major differential diagnosis for MCP include DLE, lip-fold intertrigo,

mucocutaneous candidiasis, zinc responsive dermatitis, pemphigus foliaceous,

canine epithelotropic lymphoma, adverse cutaneous drug reaction and cicatricial

pemphigoid. Lip-fold intertrigo, which also has a similar histopathological pattern,

occurs only in the lip-folds, does not cause ulceration and so can be

distinguished clinically. Zinc responsive dermatitis, pemphigus foliaceous,

pempgigus erythematosus, cicatricial pemphigoid and canine epitheliotropic

lymphoma can generally be differentiated from MCP histologically and do not

respond to antibiotic therapy. Adverse cutaneous drug reactions require careful

review of drug history to eliminate.

DLE is the most challenging disease to differentiate from MCP, due to

overlapping clinical and histological features. DLE is more likely to show basal

cell degeneration, apoptotic basal cells, a thickened basal cell membrane, and a

dermal infiltrate typically dominated by lymphocytes, plasma cells, and fewer

macrophages. Overlapping histological patterns with features of both DLE and

MCP is important because of the therapy of each disease differs considerably.

Mild cases of MCP may respond well to topical antimicrobial therapy, such as

facial antistaphylococcal ointments but more severe cases can require at least 3

to 4 weeks of systemic antibiotics the choice of which should be based on

cytological examination of the lesional skin. Very mild cases of DLE may resolve

with UV avoidance, but most also require immunomodulatory therapy or

immunosuppressive therapies.
 Case Reports

Case 1

A 4-year-old, neutered female German Shepherd Dog presented with

depigmentation, scaling, and fissuring of the dorsal nasal planum, pruritus on the

back and a few papules and pustules on the ventral abdomen. Had a previous

history of intermittent and dorsal pruritus and conjunctivitis that the referring

veterinarian had treated unsuccessfully with a combination of cephalexin 15

mg/kg once daily and prednisolone 0.5 mg/kg once every 48 hours for 1 week.

Prednisolone was then continued alone at the same dose, for a further 4½

weeks. The referring veterinarian obtained a biopsy from the nasal lesion and

submitted it for histological examination. The lesion was described as chronic

hyperplastic lymphoplasmacytic dermatitis with focal serocellular crusting,

consistent with non-specific inflammation. Therapy was then change to

doxycycline 3.4 mg/kg once daily for 7 days and an intralesional injection of

tricinolone was administered of unknown dose. The lesion did not improve and

the dog was referred.

Initial histological section revealed neutrophilic crusting with coccoid

colonies, neutrophilic exocytosis, and prominent parakeratosis, regional

hypomelanosis, mild to moderate vacuolar change, mild spongiosis in the lower

third of the epidermis, and few Civatte bodies. There was mild pigmentary

incontinence in the dermis and a marked superficial interstitial plasmacytic

infiltrate with few lymphocyte and histiocytes. These histological changes were

considered with MCP or DLE.

 Cytological examination of samples from nasal fissures reveals numerous

cocci. The dog was then treated orally with 22mg/kg cephalexin every 12 h. the

fissure on the nose and the papules on the ventral abdomen resolved after 4

weeks on this therapy, but hypopigmentation on the nasal planum remained.

Cephalexin was continued for furthered 2 weeks after which only mupirocin 2%

ointment (Bactroban®, SmithKline Beecham) was applied twice weekly for 2

weeks. The crusting of the nasal planum relapsed. Ceplalexin therapy was

repeated 22 mg/kg every 12h until 7 days beyond clinical resolution (total of 4

weeks). Antibiotic therapy then continued on a pulsed regime of 22mg/kg

cephalexin every 12 h on two consecutive days each week, along with mupirocin

ointment application twice weekly. The repeatable response to antibacterial

therapy supported the diagnosis of MCP.

Mupirocin was discontinued after a month and cephalexin pulsed therapy

continued with no relapses of clinical sign in a 13 month follow-up period. Long

term pulse antibiotic therapy was recommended to prevent relapse.

Case 2

A 7 year old, neutered female German Shepherd dog was reffered with

clinical diagnosis of AD and flea-bite hypersensitivity, supported by an

intradermal skin test showing strong positive reaction to grass and tree pollen

and flea antigen. The clinical history was of recurrent otitis and bacterial

dermatitis over a 3 year period. Physical examination there was crusting, erosion,

and ulceration of the perioral region, marked hyperpigmentation of the ventral

abdomen with multiple punctuate ulcerations, and ulcerations in a linear

configuration in the inguinal region. The dog frequently licked the abdominal skin.

The lesion failed to resolve completely on a recent 10 day course of cephalexin

22 mg/kg every 12 h.

Differential diagnosis considered for the inguinal ulcerative lesions

included bacterial infection, bullous pemphigoid, pemphigus vulgaris,

epidermolysis bullosa, linear IgA bullous dermatosis, systemic lupus

erythymatosus, erythema multiforme, vesicular lupus as seen in Collies and

Sherland sheep dogs and cutaneous drug eruption.

A biopsy of inguinal skin was taken from the edge of an ulcer for

histological examination and culture and sensitivity testing. Minimal

parakeratosis, a focal neutrophilic pustule with acantholysis, moderate

acanthosis, mild basal cell hyperplasia, moderate vacuolar change in the basal

cell laye, focal lymphohistiocytic aggregates in the basal third of the epidermis

and few Civatte bodies in the basal and suprabasilar layers were evident

histiologically. There was marked subepidermal edema, marked pigmentary

incontinence and a marked superficial dermal band-like infiltrate consisting of

histiocytes and lymphocytes. There was focal area of furunculosis with an

eosinophilic infiltrate. Staphylococcus intermedius was isolated and was sensitive

to cephalexin. After 4 weeks on cephalexin 22mg/kg every 12h, the ulcerations in

the inguinal areas and crusting on the lip margins resolved. The response to

antibacterial therapy supported a diagnosis of MCP for the perioral disease and

bacterial dermatitis for the ulcerative lesions in the inguinal area.

 Cephalexin 22 mg/kg every 12 h was continued as a pulsed therapy in two

consecutive days a week. There were no relapses during the 5 month period of

pulsed antibiotic therapy.

Case 3

A 3-year-old, neutered male GermanShepherd dog presented in 1996 with

a history of pruritus and recurrent bacterial dermatitis. Suffered from intermittent

otitis externa and recurrent superficial bacterial infections that were responsive to

antimicrobial therapy, and was diagnosed with AD. The skin infection recurred

every 2-3 months since first presentation in 1996, manifesting perioral dermatitis

and erosion, fissuring and crust involving nares and lip margins (MCP) and

ulceration of the axillae and inguinal areas and bacterial pododermatitis. The

lesion was always responsive to antibiotics. ASIT was commenced in 1997 but

was discontinued after 4 years because it failed to prevent frequent relapses of

bacterial skin infection and otitis externa. Pulsed therapy with cephalexin

(22mg/kg every 24 h 2 days /week) prevented relapsed of MCP for a period of

about 1 year after ASIT ceased. On pulsed cephalexin therapy bacterial

pododermatitis relapsed, was then successfully treated with daily enrofloxacin

and then pulsed therapy continued with enrofloxacin (5mg/kg every 24 h, 2 days

/week). After 5 months of pulsed therapy with enrofloxacin , there was relapsed

of crusting, fissuring and depigmentation of the lips. Relapsing MCP due to

bacterial resistance considered in addition to differential diagnosis.

 In 2001, a biopsy was obtained from deep tissue of lesional skin for

culture, sensitivity testing and histological examination. The lip margin showed

diffused mild parakeratosis, hypergranulosis, mild to moderate acanthosis, focally

mild to moderate neutrophilic exocytosis, regional to diffuse basal spongiosis and

few Civatte bodies. There was regional obscurement of the dermoepidermal

junction, moderate to marked pigmentary incontinence, regional subepidermal

edema and a band-like infiltrate of plasma cells, lymphocytes, focal aggregates

of neutrophils and a moderate perivascular infiltrate consisting of mast cells. This

infiltrate extended to surround some adnexal structures and follicles.

Beta-hemolytic Streptococcus sp. and Staphylococcus aureus were

isolated, both of which were found to be resistant to enrofloxacin and

clindamycin. On the basis of bacterial culture and sensitivity testing, treatment

with oral amoxicillin and clavulanic acid began at 14 mg/kg every 12 h for 6

weeks. Lesion resolved on this therapy. Pulse therapy continued with the same

dose of amoxicillin and clavulanic acid two consecutive days per week. The

histopathological changes, in addition to the clinical presentation and response to

antibiotic therapy supported a diagnosis of relapsing MCP. There was no relapse

of the lesion while on pulsed therapy with amoxicillin and clavulanic acid in 10

month follow up period. Continuation of pulsed therapy was recommended.

Discussion

The case presented, the diagnosis of MCP was based on clinical

presentation, cytological and histological examination, positive bacterial culture,

and resolution of lesions with antibiotic therapy selected on basis of cytological

examination and or bacterial culture and sensitivity testing. The three dogs were

German Shepherd Dogs, consistent with previous reports that this breed is over-

represented in cases with MCP.

MCP is commonly reported to be a relapsing disease. Cases 1 and 3 had

documented relapse every 1-3 months, but pulse antibiotic therapy have

prevented relapse for 13 and 10 months respectively. In case 2, pulsed therapy

was discontinued after 5 months and the dog remain lesion free for a further 12

months with no medication. Pulsed antibiotic regimen have previously been

reported to be successful in preventing relapsed of deep pyoderma in German

Shepherd Dogs, but this is the first report of successful, long term management

of MCP with a pulsed antibiotic therapy. Case 2 did not relapse after pulse

therapy ceased is not known, however, it should be noted that the recurrent

folliculitis and otitis that had previously occurred in association with MCP lesion

also resolved. Case 2 was atopic dog, and tempting to attribute the control of

MCP to control the AD from the geographical reduction in allergen exposure.

Histopathological findings in these three cases of MCP included Civatte

bodies, basal cell vacoulation, refional obscurement of the basal cell layer and

lichenoid lymphoplasmitic inflammation. Overlapping histopathological and

clinical features between MCP and DLE have been reported.

 Two of the three dogs, had ulcerative dermatitis affecting the inguinal and

auxillary areas. Clinically, the inguinal ulceration was similar to that seen at the

mucocutaneous site, apart from the absence of crusting and the presence of

peri-ulcer hyperpigmentation. It is possible that the self trauma to the inguinal

area and axillary region prevented crust formation. MCP other intertriginous

zone, the vaginal folds, rarely has crusting. The hyperpigmentation is consisted

with chronic inflammation. Histopathological examination of mucocutaneous site

and inguinal site showed similar features. This together with the repeatable

resolution of the intertriginous ulceration with antibiotic therapy, suggest bacterial

etiology.

MCP is a manifestation of a superficial bacterial infection is clinically

distinct from more typical lesion of superficial bacterial infection such as papules

and pustules. The pathogenic mechanism causing ulceration in MCP remains

unclear. The inguinal and axillary lesions were clinically more similar to those

seen MCP than the typical reported lesion of superficial bacterial infections.

There may be a common pathogenic mechanism in these lesions. Bacterial by-

product on the skin can augment cutaneous inflammation via a number of

mechanisms, including bacterial hypersensitivity, super-antigen-mediated

lymphocytes activation and non-specific mechanism. Epidermal injury may then

result in ulceration due to direct cell death from bacterial by-product or

immunological mechanisms. Keratinocytes play a role in initiating cell-mediated

immune response by cytokine release and adhesion molecule expression and

can be activated in the presence of bacterial superantigen. The immune-

mediated features evident histologically may be cause by bacterial activation of

keratinocytes and subsequent immune response. The restricted distribution of

lesion in these cases may reflect the normal carriage and sporadic colonization

sites of bacteria.

MCP appears to be a manifestation of superficial bacterial infection in

some dogs, particularly German Shepherd Dogs. In cases of recurrent MCP one

should consider underlying diseases known to predispose dogs to recurrence

superficial bacterial infections. Superficial bacterial infection in an known

manifestation of AD in dogs. Two of the three cases presented were diagnosed

with AD on clinical sign and supportive positive intradermal allergy test. In the

third case, no investigation was conducted for underlying allergy although there

was clinical and historical support for a diagnosis of hypersensitivity disease. It is

worth considering that MCP may be a clinical manifestation of AD in some dogs.

Control of relapsing MCP by successful management of AD would support a

causal role of AD in MCP. However, in the one case which immunotherapy was

employed, it failed to prevent the relapse of MCP.

Conclusion

Cutaneous bacterial infection in German Shepherd Dogs may present as

erosions and ulceration with or without crusting at mucocutaneous junction and in

axillary and inguinal intertriginous regions. Histological features in common with

immune-mediated disease may be seen in lesional biopsies from these sites.

The lesions are antibiotic responsive in relapsing cases can be successfully

manage with a pulsed antibiotic regimen.

Cytological examination and antimicrobial therapy prior to biopsy is

recommended for erosive and ulcerative crusting lesion involving the

mucocutaneous junction or axillary and inguinal skin in dogs. The possibility of

MCP being a manifestation of atopic disease warrants further investigation.